Phenylacetylphenyl carbamates



United States Patent 3,337,608 PHENYLACETYLPHENYL CARBAMATES Edward L.Schumann, Portage Township, Kalamazoo County, Mich., assignor to TheUpjohn Company,

Kalamazoo, Mich., a corporation of Delaware No Drawing. Filed Mar. 18,1963, Ser. No. 266,089 3 Claims. (Cl. 260479) This invention relates tonew and useful chemical compounds and more particularly tophenylacetylphenyl carbamates which are useful as sedatives andanti-inflammatory agents.

The novel compounds of the present invention are represented by thefollowing structural formulas:

wherein R and R taken individually represent a member selected from thegroup consisting of hydrogen, alkyl of from 1 to 4 carbon atoms,inclusive, and alkenyl of from 3 to 4 carbon atoms, inclusive, and takentogether with N represent saturated heterocyclic amino selected from thegroup consisting of unsubstituted and monoand polyalkyl substitutedpiperidino, morpholino, thiamorpholino, pyrrolidino, hexamethylenimino,heptamethylenimino, ,octamethylenimino, and homomorpholino wherein eachalkyl is of from 1 to 4 carbon atoms, inclusive; each of X and Y is fromzero to 3 alkoxys of from 1 to 2 carbon atoms, inclusive; X is selectedfrom the group consisting of from Zeroto 2 halogens and from zero to 2alkyls of from 1 to 3 carbon atoms, inclusive;

and Y is selected from the group consisting of from zero to'l halogen,from zero to 1 nitro, and from zero to l Jmethyl; and R and R areselected from the group consisting of phenyl, tolyl, and methoxyphenyl.

Representative groups within the scope of the present invention include:alkyl, e.g., methyl, ethyl, propyl, isopropyl, butyl, and isobutyl;alkenyl, e.g., allyl, methallyl, and crotyl; halogen, e.g., fluoro,chloro, bromo, and iodo;

.saturated heterocyclic amino e.g., piperidino, morpholino,.thiamorpholino, pyrrolidino, hexamethylenimino, heptamethylenimino,octamethyleni-mino, homomorpholino, 2- methylhexamethylenimino, 2,2dibutylhexamethylenimino, 3,6-dimethylhexamethylenimino,2ethylmorpholino, 2-ethyl-5-rnethylmorpholino, 3,3-dimethylmorpholino,3- methylthiamorpholino, 2,3,5,6-tetrarnethylthiamorpholino,2,3,6-trimethylthiamorpholino, 2-methylpiperidino, 3- methylpiperidino,4-methylpiperidino, 2 butylpiperidino,

2-propylpiperidino, 4-isopropylpiperidino, 3,4-diethylpiperidino,2-sec.butylpyrrolidino, 2,2-dimethylpyrrolidino, 2- ethylpyrrolidino,3,4-dirnethylpyrrolidino, and 2-isopropylpyrrolidino; and alkoxy, e.g.,methoxy and ethoxy.

The starting material for the preparation of the compounds of thepresent invention is a hydroxyacetophenone of the formula:

III

Patented Aug. 22, 1967 and X X IV Compounds of the present invention ofFormulas I and II wherein R is hydrogen and R is alkyl or alkenyl (i.e.,monoalkyland monoalkenylcarbamates) are readily prepared by condensing ahydroxyacetophenone of the Formulas III and IV with an alkyl or alkenylisocyanate, for example, methyl, ethyl, propyl, isopropyl, butyl,isobutyl allyl, and crotyl isocyanate, in the presence of an inertorganic solvent, for example, diethyl ether, diiso- .propyl ether,dioxane, toluene, and the like. The reactants are preferably mixed inequimolar proportions, but, if desired, an excess of either reactant canbe used. The reaction proceeds at temperatures between about 15 C. andabout C. and can be accelerated by adding a small amount of a base suchas triethy'lamine. Illustratively, the carbamates are readily obtainedin many instances by allowing the reaction mixture to stand overnight atabout 25 C. The product is recovered by conventional means such asfiltration, or concentration of the reaction mixture followed byfiltration, washing and recrystallization. a

The compounds of Formulas I and II are also prepared by reacting acompound of Formulas III and IV, preferably in the form of an alkalimetal salt, e.g., sodium or potassium salt, with phosgene to form thecorresponding chloroformate of the formulas:

wherein R R4, X, X, Y, and Y are as hereinbefore defined, and thenreacting the chloroformate with ammonia, a monoalkylamine, amonoalkenylamine, a dialkylamine, a dialkenylamine, analkylalkenylamine, or a saturated heterocyclic amine such asunsubstituted and monoand polyalkyl substituted piperidine, morpholine,thiamorpholine, pyrrolidine, hexamethylenirnine, heptamethylenimine,octamethylenimine, and homomorpholine wherein each alkyl is of from 1 to4 carbon atoms, inclusive.

The chloroformate of Formulas V and VI is prepared by mixing a compoundof Formulas III and IV, an aqueous solution of a base, for example,sodium or potassium hydroxide, and a solution of phosgene in an inertorganic solvent, for example, toluene, benzene, diethyl ether, and thelike. This reaction is exothermic and is advantageously carried out attemperatures between about 30 C. and about +30 C. The phosgene: organicsol vent solution is added slowly and with mixing to prevent localizedheating or undesirable temperatures above 30 C. The chloroformate, thusformed, accumulates in the organic phase and the aqueous phase isseparated. The chloroformate can be isolated and purified byrecrystallization or it can be used without further purification in thepreparation of the carbamates of the present invention.

The reaction of an amine of the kind noted above and the chloroformateis carried out in the presence of a solvent, for example, water, diethylether, and dioxane. The reaction is advantageously carried out attemperatures in the range of about C. to about 50 C. The rate ofreaction is slow at temperatures below about 10 C.; and at temperaturesabove about 50 C., the ammonia or amine can volatilze and decompositionof the chloroformate intermediate or carbamate product can occur.Stoichiometrically, the reaction requires one mole of amine for eachmole of chloroformate. However, the reaction produces one mole ofhydrogen chloride, so an excess of the amine, preferably about at leastone mole excess, or another suitable acid acceptor, for example,triethylamine, pyridine, picoline, sodium hydroxide, and the like shouldbe employed. The carbamate product of Formula I or II is recovered byconventional methods, for example, filtering off any solids, removingthe solvent, washing and recrystallization from a suitable solvent.

Alternatively, compounds of Formula I and II can be prepared by reactinga carbamyl halide, for example, dimethylcarbamyl chloride,propylcarbamyl chloride, and the like, with a hydroxyacetophenone havingFormulas III and IV.

The starting hydroxyacetophenones of Formulas III and IV can be preparedby a Friedel-Crafts reaction between a phenol of the formula:

X X VII wherein X and X are as hereinbefore defined, and an acid halideof the formula:

@orn-onm X Y VIII and ll /OHC-Hal R4 IX wherein Hal is chlorine orbromine, and R R Y, and Y are as hereinbefore defined.

The following examples are illustrative of the preparation of compoundsof the present invention but are not to be construed as limiting.

EXAMPLE 1 4-phenylacetylphenyl methylcarbamate A solution of 21.2 g. of(0.1 mole) of 4'-hydroxy-2- phenylacetophenone in 300' ml. of anhydrousether and 50 ml. of anhydrous acetone was treated with 5.7 g. (0.1 mole)of methyl isocyanate and 2 drops of triethylamine, then stirredovernight at about 25 C. Solvent was removed under reduced pressure andthe solidified residue was recrystallized twice from methanol to give 9g. of 4 phenylacetylphenyl methylcarbamate as white crystals whichmelted at 119120 C.

Analysis.Calcd. for C H NO C, 71.36; H, 5.62; N, 5.20. Found: C, 71.20;H, 5.63; N, 5.30.

EXAMPLE 2 2-br0m0-4-flu0r0-6-phenylacetylphenyl ethylcarbamate Followingthe procedure of Example 1, but substituting3'-bromo-5'-fluoro-2-hydroxy-2 phenylacetophenone for the4-hydroxy-2-phenylacetophenone and ethyl isocyanate for methylisocyanate, Z-bromo-4fluoro-6-phenylacetylphenyl ethylcarbamate isobtained.

EXAMPLE 3 2-(4-i0d0phenylacetyl) phenyl ethylcarbamate Following theprocedure of Example 1, but substituting2-hydroXy-2-(4-iodophenyl)acetophenone for the4'-hyclroxy-2-phenylacetophenone and ethyl isocyanate for methylisocyanate, 2-(4-iodophenylacetyl)phenyl ethylcarbamate is obtained.

EXAMPLE 4 Z-chl0r0-4-phenylacetylphenyl propylcarbamate Following theprocedure of Example 1, but substituting3-chloro-4-hydroxy-2-phenylacetophenone for the4'-hydroxy-2-phenylacetophenone and propyl isocyanate for methylisocyanate, 2-chloro-4-phenylacetylphenyl propyl: carbamate is obtained.

EXAMPLE 5 2-fluoro-6-iodo-4-phenylacetylphenyl isopropylcarbamateFollowing the procedure of Example 1, but substituting3'-fiuoro-4-hydroxy-5'-iodo-2-phenylacetophenone for the4'-hydroxy-2-phenylacetophenone and isopropyl isocyanate for methylisocyanate, 2-fiuoro-6-iodo-4-phenylacetylphenyl isopropylcarbamate isobtained.

EXAMPLE 6 2,3-dimethoxy-6-phenylacetylphenyl isopropylcarbamateFollowing the procedure of Example 1, but substituting3',4-dimethoxy-2-hydroxy-2-phenylacetophenone for the4'-hydroxy-Z-phenylacetophenone and isopropyl isocyanate for methylisocyanate, 2,3-dimethoxy-6-phenylacetylphenyl isopropylacarbamate isobtained.

EXAMPLE 7 3,5-dimeth0xy-4- (4-meth0xyphenylacetyl)phenyl butylcarbamateFollowing the procedure of Example 1, but substituting 2,6dimethoxy-4-hydroxy 2-(4-methoxyphenyl) acetophenone for the4-hydroxy-2-phenylacetophenone and butyl isocyanate for methylisocyanate, 3,5-dimethoxy- 4-(4-methoxyphenylacetyl)-phenylbutylcarbamate is obtained.

EXAMPLE 8 4-(4-meth0xyphenylacetyl)phenyl isobutylcarbamate Followingthe procedure of Example 1, but substituting4-hydroxy-2-(4-methoxyphenyl)acetophenone for the 4-hydroxy-Z-phenylacetophenone and isobutyl isocyanate for methylisocyanate, 4-(4-methoxyphenylacetyl)phenyl iso butylcarbamate isobtained.

EXAMPLE 9 S-methoxy-Z-(4-nitrophenylacetyl)phenyl allylcarbamateFollowing the procedure of Example 1, but substituting2-hydroxy-4-methoxy-2-(4-nitrophenyl) acetophenone for the4-hydroxy-2-phenylacetophenone and allyl isocyanate for methylisocyanate, 5-methoxy-2-(4-nitrophenylacetyl)phenyl allylcarbamate isobtained.

EXAMPLE 10 2 -iso propyl-4-methoxy-5 -methyl-6 -pheny lacetylphenylcrotylcarbamate EXAMPLE 11 2-phenylacetylphenyl dimethylcarbamate A. 2phenylacetylphenyl chl0r0f0rmate.42.4 grams (0.2 mole) of2-hydroxy-2-phenylacetophenone and 8.0 grams (0.2 mole) of sodiumhydroxide are added to 150 ml. of water. To this aqueous solution isadded a solution of 19.8 grams (0.2 mole) of phosgene in m1. of to1u r Jene, prepared by bubbling phosgene into toluene at l C. Thephosgeneztoluene solution is added slowly with mechanical stirring whilemaintaining the temperature below 25 C. The reaction mixture is stirredfor 1.5 hours and filtered to remove solids. The aqueous layer isseparated from the organic layer in a separatory funnel and the organiclayer washed with 200-ml. portions of aqueous potassium hydroxidesolution. The toluene solution is washed with water until neutral andthen dried over anhydrous sodium sulfate. The toluene isremoved bydistillation under reduced pressure to leave Z-phenylacetylphenylchloroformate as a residue.

B. 2 phenylacetylphenyl dimethylcarbamate.-To a solution of 27.4 grams(0.1 mole) of 2-phenylacetylphenyl chloroformate in 200 ml. of anhydrousdiethyl ether is added 9.0 grams (0.2 mole) of dimethylamine dissolvedin 100 ml. of anhydrous ether. The reaction flask is stirred during theaddition to prevent localized heating. The reaction mixture is allowedto stand overnight during which time a precipitate forms. Theprecipitate is removed by filtration and the ether by means ofdistillation under reduced pressure to provide 2-phenylacety1phenyldimethylcarbamate.

EXAMPLE 12 3,5-dimeth0xy-4- (4-methoxyphenylacetyl) -2-methylphenylcarbamale Following the procedure of Example 11, Part A, substituting2,6' dimethoxy-4-hydroxy-2-(4-methoxyphenyl)-3-methylacetophenone forthe 2'-hydroxy-2-phenylacetophenone, the respective chloroformate isobtained. Following the procedure of Part B, commencing with 3,5-dimethoxy 4 (4-methoxyphenylacetyl)-2methylphenyl chloroformate andsubstituting ammonia for dimethyla mine, 3,5dimethoxy-4-(4-methoxyphenylacetyl)-2-methylphenyl carbamate isobtained.

EXAMPLE 13 2,3-dimeth0xy-6- (3,4-dimethoxyphenylacetyl) -phenylmethylallylcarbamate Following the procedure of Example 11, Part A,substituting 3',4 dimethoxy2-(3,4-dimethoxyphenyl)-2-hydroxyacetophenone for the2'-hydroxy-2-phenylacetophenone, the respective chloroformate isobtained. Following the procedure of Part B, commencing with2,3-dimethoxy- 6-(3,4-dimethoxyphenylacetyl)phenyl chloroformate andsubstituting Inethylallylamine for dimethylamine, 2,3-dimethoxy 6(3,4-dimethoxyphenylacetyl)phenyl methylallylcarbamate is obtained.

EXAMPLE 14 3,5-dieth0xy-2- (3-elhoxy-5-meth0xyph enylacetyl) phenylmethylethyl ca rbamate' EXAMPLE 15 IS-methoxy-Z-(3-chloro-2,4,6-trimethoxyphenylacetyl) phenyldicrotylcarbamate Following the procedure of Example 11, Part A,substitutin g 2- 3-chloro-2,4,6-trimethoxyphenyl) -2'-hydroxy-4'-methoxyacetophenone for the 2'-hydroxy-2-phenylacetophenone, therespective chloroformate is obtained. Following the procedure of Part B,commencing with S-methoxy- 2(3-chloro-2,4,6-trimethoxyphenylacetyl)phenyl chloroformate andsubstituting dicrotylamine for dimethylamine, 5 methoxy 2(3-ch1oro-2,4,6-trimethoxyphenylacetyl) phenyl dicrotylcarbamate isobtained.

6 EXAMPLE 16 4-methyI-Z-phenylacetylphenyl letramethylenecarbamaze isobtained.

EXAMPLE 17 3-methyl-4-phenylaoetylphenyl pentamethylenecarbamateFollowing the procedure of Example 11, Part A, substituting4-hydroxy-2-methyl-2-phenylacetophenone for the2-hydroxy-2-phenylacetophenone, the respective chloroformate isobtained. Following the procedure of Part B, commencing with3-methyl-4-phenylacetylphenyl chloroformate and substituting piperidinefor dimethylamine, 3- methyl-4-phenylacetylphenylpentamethylenecarbamate is obtained.

EXAMPLE 18 2-flu0r0-4-phenylacetylphenyl hemmethylenecarbamate Followingthe procedure of Example 11, Part A, substituting3-fluoro4-hydroxy-2-phenylacetophenone for the2-hydroxy-Z-phenylacetophenone, the respective chloroformate isobtained. Following the procedure of Part B, commencing with2-fluoro-4-phenylacetylphenyl chloroformate and substitutinghexamethylenimine for dimeth' ylamine,2-fiuoro-4-phenylacetylpheny1hexamethylenecarbamate is obtained.

EXAMPLE 19 2-(2,5-dimethoxyphenylaloetyl)-3,4,5-trimethoxyphenylhepzamethy lenecarbamate Following the procedure of Example 11, Part A,substituting 2 (2,5dimethoxyphenyl)-6'-hydroxy-2',3',4'-trimethoxyacetophenone for the2-hydroxy-Z-phenylacetophenone, the respective chloroformate isobtained. Following the procedure of Part B, commencing with 2-(2,5-dimethoxyphenylacetyl) 3,4,5-trirnethoxyphenyl chloroformate andsubstituting heptamethyle-nimine for dimethylamine,2-(2,5-dimethoxyphenylacetyl)-3,4,5-trimethoxyphenylheptamethylenecarbamate is obtained.

EXAMPLE 20 3,5-diethoxy-2- (4-eth0xyphenylacelylJ l-methoxyphenyloctamethylenecarbamate Following the procedure of Example 11, Part A,substituting 2,4' diethoxy-2-(4-ethoxyphenyl)-6-hydroxy-3-methoxyacetophenone for the 2'-hydroxy-2-phenylacetophenone, therespective chloroformate is obtained. F ollowing the procedure of PartB, commencing with 3,5-diethoxy-2-(4-ethoxyphenylacetyl)-4-methoxyphenylchloroforrnate and substituting octamethylenimine for dimethylamine, 3,5diethoxy 2-4-ethoxyphenylacetyl)-4- methoxyphenyl octamethylenecarbamateis obtained.

EXAMPLE 21 4-(4-ethoxyphenylacetyl) phenyl (1,1-dimethyltezramethylene)carbamate Following the procedure of Example 11,Part A, substituting 2-(4-ethoxyphenyl)-4-hydroxyacetophenone for the2'-hydroxy-2-phenylacetophenone, the respective chloroformate isobtained. Following the procedure of Part B, commencing with4-(4-ethoxyphenylacetyl)phenyl chloroformate and substituting2,2dimethylpyrrolidine for dimethylamine, 4-(4-ethoxyphenylacetyl)phenyl(1,1- dimethyltetramethylene)carbamate is obtained.

7 EXAMPLE 22 3,5-diethoxy2-(4-eth0xy-3-methoxyphenylacetyl)phenyl (1-methyl pen tamethy l ene) carbamate Following the procedure of Example11, Part A, substituting 2',4'-diethoxy-2-(4-ethoxy-3-methoxyphenyl)-6-hydroxyacetophenone for the 2-hydroxy-2-phenylacetophenone, therespective chloroformate is obtained. Following the procedure of Part B,commencing with 3,5- diethoxy 2 (4 ethoxy-3-methoxy henylacetyl)phenylchloroformate and substituting Z-methylpiperidine for dimethylamine,3,5-diethoxy-2-(4-ethoxy-5-methoxyphenylacetyl)phenyl(l-methylpentamethylene)carbamate is obtained.

Using the following hydroxyacetophenones in Examples 1 thru 22, thecorresponding carbamatees are obtained:

4'-chlor0-2'-hydroxy-2-phenyl-,

4',6-dimethoxy-2- (2,3 -dimethoxyphenyl -2-hydroxy-,

4,6'-dimethoxy-2'-hydroXy-2- Z-methoxyphenyl 4,6-dimethoxy-2-hydroxy-2-(4-methoxyphenyl 4,6-dimethoxy-2'-hydroxy-2- (4-methoxyphenyl -2-methyl-,

4',6-dimethoxy-2-hydroxy-2- (Z-methoxyphenyl -3 methyl-,

2,4-dimethoxy-6-hydroxy-2- 4-methoxyphenyl) )-3 methyl-,

2,4'-dimethoxy-6'-hydroxy-2- 2-methoxyphenyl) -3 methyl,

4,6-dimethoxy-2'-hydroxy-3 '-methyl-2- 4-nitrophenyl4',6'-dimethoxy-2-hydroxy-3 -methyl-2-phenyl-,

3',4-dimethoxy-2-hydroxy-2-phenyl-,

4,5-dimethoxy-2-hydroxy-2-phenyl-,

5 ,6-dimethoxy-2-hydroxy-2-phenyl-,

3'-hydroxy-5 '-isopropyl-6-methoxy-2'-methyl-2-phenyl-,

2-hydroxy-4'-methoxy-2- 2-methoxyphenyl 2'-hydroxy-4'-methoxy-2-(4-methoxyphenyl 6'-hydroxy-2- Z-methoxyphenyl -2',3 ',4'-trirnethoxy-,

2-hydroXy-5 -methoxy-2-phenyl-,

-hydroxy-6-methoxy-2-phenyl-, and2'-hydroxy-4'-methoxy-2-phenylacetophenones.

In following the procedures of Examples 11 thru 22 with the abovehydroxyacetophenones, the corresponding chloroformates are alsoobtained.

EXAMPLE 23 4-diphenylacetylphenyl methylcarbamate A mixture of 28.8 g.(0.1 mole) of 4'-hydroxy-2,2-diphenylacetophenone, 250 ml. of toluene,5.7 g. (0.1 mole) of methyl isocyanate, and 3 drops of triethylamine washeated under reflux for 5 hr., then refrigerated. The mixture wasfiltered to remove unreacted starting material and the filtrate wasevaporated to dryness under reduced pressure. Recrystallization of theresidue from chloroform-technical hexane, twice from ethylacetate-technical hexane, and again from chloroform-technical hexanegave 10.3 g. of 4-diphenylacetylphenyl methylcarbamate as soft Whiteneedles, M.P. 104-105 C.

EXAMPLE 24 2-(di-p-zolylacetyhphenyl methylcarbamate Following theprocedure of Example 23, substituting 2,2 dip-toyl-2'-hydroxyacetophenone for the 2,2-diphenyl 4hydroxyacetophenone, 2 (di-p-tolylacetyl) phenyl methylcarbamate isobtained.

EXAMPLE 25 Z-diphenylacetylphenyl miethylcarbamaze Following theprocedure of Example 23, substituting 2,2 diphenyl 2 hydroxyacetophenonefor the 2,2-diphenyl-4-hydroxyacetophenone, methylcarbamate is obtained.

EXAMPLE 26 2- (di-4-meth0xypheny lacetyl -5-methoxyphenyl methylcarbamaie Z-diphenylacetylphenyl Following the procedure of Example23, substituting 2,2 di 4 methoxyphenyl-2-hydroxy-4-methoxyacetophenonefor the 2,2-diphenyl-4-hydroxyacetophenone, 2- (di-4-methoxyphenylacetyl-5 -methoxyphenyl methylcarbamate is obtained.

EXAMPLE 27 4-phenylacetylphenyl (3-0xapentamethylene) carbamate4-phenylacetylphenyl (3-flziapentamethylene)- carbamate Following theprocedure of Example 27, Part B, commencing with 4-phenylacetylphenylchloroformate and substituting thiamorpholine for morpholine,4-phenylacetylphenyl (3-thiapentamethylene)carbarnate is obtained.

EXAMPLE 29 4-phenylacetylphenyl (3-oxahexamethylene) carbamate Followingthe procedure of Example 27, Part B, commencing with4-phenylacetylphenyl chloroformate and substituting homomorpholine formorpholine, 4-phenylacetylphenyl (3-oxahexamethylene)carbamate isobtained.

Following the procedures of Examples 3, 4, 5, 7, 8, 9, and 10,substituting the hydroxyacetophenones employed therein by2,2-diphenyl-4'-hydroxyacetophenone, 2,2-diphenyl 2 hydroxyacetophenone,2,2-di-p-tolyl-2-hydroxyacetophenone, and2,2-di-4-methoxyphenyl-2'-hydroxy-4-methoxyacetophenone, thecorresponding ethyl, propyl, isopropyl, butyl, isobutyl, allyl, andcrotylcarbamates are obtained.

Following the procedure of Example 11, Part A, substituting the2-hydroxy-2-phenylacetophenone by 2,2-di phenyl-4-hydroxyacetophenone,2,2 diphenyl 2' hydroxyacetophenone, 2,2-di-p-tolyl 2'hydroxyacetophenone, and 2,2-di-4-methoxyphenyl-2-hydroxy-4'methoxyacetophenone, the corresponding 4-diphenylacetylphenyl, 2diphenylacetylphenyl, 2 (di-p-tolylacetyl) phenyl, and2-(di-4-methoxyphenylacetyl) 5 methoxyphenyl chloroformates areobtained, which by the procedures of Part B of Examples 12, 11, 13, 14,15, 16, 17, 18, 19, 20, 21, 22, and 27, and Examples 28 and 29, areconverted to the corresponding unsubstituted carbamates and dimethyl-,methy-lallyl-, methylethyl-, dicrotyl-, tetramethylene-,pentamethylene-, hexamethylene-, heptamethylene-, octamethylene-,1,1-dimethyltetramethylene) l-methylpentamethylene (3-oxapentamethylandtopical administration. For oral administration the compositions cantake the form of tablets, capsules, boluses, pills, powders, granules,feeds, syrups, elixirs, and the like. Topical administration can be inthe form of ointments, creams, lotions, solutions, suspensions, sprays,and powders. For parenteral administration sterile solutions andsuspensions can be prepared in vehicles containing water, ethanol,glycerol, propylene glycol,

polyalkylene glycols, vegetable oils, and the like.

The compositions, in the appropriate form, can be administered orallyand parenterally for systemic treatment, or topically such as on theskin, or locally such as for treating mastitis in cattle, orparenterally for local treatment such as injection into the jointcavity, tendon sheath, and bursa.

The compositions provide the veterinarian with a method for treatinginflammation in large and small animals as well as birds and poultry.The animals and birds can be commercial animals raised for profit aswell as animals kept for pets or research. Inflammatory conditions whichcan be treated include, but are not limited to, enteritis, iritis,retained placenta, laminitis, rheumatoid and traumatic arthritis,osteoarthritis, periostitis, tendonitis, tenosynovitis, bursitis, andrnyositis.

The dosage of the compounds of the present invention depends upon theparticular subject treated and the subjects age, weight and condition,as well as the particular condition being treated, its severity androute of administration. In general a dose of 3 mg. to 45 mg. per kg. ofbody weight given daily in single or divided doses, or 250 to 3000 mg.per day, embraces the effective therapeutic dosage for most conditionsfor which the said compounds are effective.

Advantageously the compounds of the present invention do not have theundesirable side-effects encountered with steroid and other types ofanti-inflammatory agents. For example, there is no marked water, sodiumor potassium retention nor is there the development of gastriculceration or other distress.

The following examples illustrate the preparation of pharmaceuticaldosage forms but are not to be considered as limiting.

EXAMPLE 30 One thousand scored tablets for oral administration, eachcontaining 500 mg. of 4-phenylacetylphenyl methylcarbamate are preparedfrom the following types and amounts of ingredients:

Gm. 4-phenylacetylphenyl methylcarbamate 500 Lactose 150 Corn starch 65Magnesium stearate 25 Light liquid petrolatum 3 EXAMPLE 31 One thousandcc. of a sterile aqueous suspension for parenteral administration andcontaining 250 mg. of 4-phenylacetylphenyl methyl carbamate per cc. isprepared from the following types and amounts of ingredients:

4-phenylacetylphenyl methylcarbamate gm 250 Polyethylene glycol 4000,U.S.P. gm 30 Procaine hydrochloride gm 20 Myristyl gamma picoliniumchloride gm 0.2 Water for injection, q.s. cc 1000 10 EXAMPLE 32 Onethousand cc. of an aqueous syrup suspension for oral administrationcontaining 500 mg. of 4-phenylacetylphenyl methylcarbamate in each 5 cc.dose is prepared from the following types and amounts of ingredients:

4-phenylacetylphenyl methylcarbamate .gm Citric acid gm 2 Benzoic acidgm 1 Sucrose gm 700 Tragacanth gm 5 Oil of lemon cc 2 Deionized water,q.s. cc.. 1000 EXAMPLE 33 500 lbs. of a composition for feeding turkeyswith enteritis are prepared from the following types and amounts ofingredients:

4-phenylacetylphenyl methylcarbamate gm 75 Ground oats lb 30 Meat andbone scraps 50%* lb 30 Fish meal 60%* lb 20 Alfalfa meal, dehydrated17%* lb 30 Ground corn lb 158 Wheat bran 1b 15 Wheat std. midds. lb 30Soybean oil meal 50%* lb 50 Dicalcium phosphate lb 9.5 Calcium carbonatelb 14 Trace mineralized salt lb 2.5 Yellow fat lb 10 Vitamin D premix lb0.3 B-vitamin supplement lb 0.4-5 Trace mineral supplement lb 0.3

* The percentages refer to the percent of protein present.

EXAMPLE 34 Following the procedures of Examples 30 to 33, inclusive,compositions are similarly prepared substituting 'an equal amount of acompound prepared according to Examples 2 to 29, inclusive, for the4-phenylacetylphenyl methylcarbamate shown.

What is claimed is:

1. A compound selected from the group consisting of compounds of theformula:

and of the formula:

XX II wherein R and R t-aken individually represent a member selectedfrom the group consisting of hydrogen, alkyl of from 1 to 4 carbonatoms, inclusive, and alkenyl or from 3 to 4 carbon atoms, inclusive,and taken together with N represent saturated heterocyclic aminoselected from the group consisting of unsubstituted and monoandpolyalkyl substituted piperidino, morpholino, thiamorpholino,pyrrolidino, hexamethylenimino, heptamethylenirnino, octamethylenimino,and homomorpholino wherein each alkyl is of from 1 to 4 carbon atoms,inclusive; each of X and Y is from zero to 3 alkoxys of from 1 to 2carbon atoms, inclusive; X is selected from the group consisting of fromzero to 2 halogens and from zero to 2 alkyls of from 1 to 3 carbonatoms, inclusive; Y is selected from the group consisting of from zeroto 1 halogen, from zero to 1 nitro, and from zero to 1 methyl; and R andR are selected from the group consisting of phenyl, tolyl, andmethoxyphenyl.

2. 4-phenylacetylphenyl methylcarbamate.

3. 4-diphenylacetylphenyl methylcarbamate.

References Cited 12 Spiegler 260-463 Lambrech 260-479 Hopkins et al.260-463 X Berger et al. 260-463 X Finke et al. 260-463 X S-hulgin260-479 Moore et al. 260-479 Strube 260-479 Schumann 260-479 OTHERREFERENCES Barnes et al.: Journal of Pharmacy and Pharmacology, vol. 13,pp. 3948 (1961).

Brostoff et al.: Journal of Pharmacy and Pharmacology, vol. 13, pp.65-71 (1961).

Dinglinger: Justus Liebigs Annalen der Chemie, vol. 311, pp. 147-153(1900).

Hodgson et al.: Biochimica et Biophysica Acta, vol. 42,

LORRAINE A. WEINBERGER, Primary Examiner,

CHARLES B. PARKER, RICHARD K. JACKSON,

UNITED STATES PATENTS 2,370,570 2/1945 Muskat 260-463 2,455,652 12/1948Bralley et al. 260463 X 2,485,550 10/1949 Aeschlimann et al. 260-4792,524,185 10/1950 Zirna 260-479 2,677,698 5/1954 Deutschman et al..260-479 2,787,631 4/1957 Stevens 260-463 2,855,436 10/ 1958 Rekker.2,858,328 10/1958 Beaver et al.

Examiners.

F. D. HIGEL, I. R. PELLMAN, Assistant Examiners.

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF COMPOUNDS OF THEFORMULA: